Central hypoxic-hypercapnic interaction in mild hypoxia in man

Hypoxic-hypercapnic interaction in mild hypoxia was studied in 12 healthy males. Steady state ventilatory responses to hypercapnic-hypoxia were obtained as the difference in ventilation between hypoxia (mean values ± S.D. of =7.36±0.20 kPa or of 7.10 ±0.41 kPa) and hyperoxia ( >26.7 kPa) with the same degree of hypercapnia ( 6.12±0.22 kPa). On the other band, withdrawal responses were obtained as the magnitude of depression in ventilation caused by two bicaths of O₂ from the above mentioned hypoxic hypercapnia. Averaged and were 9.57±5.45 and 6.45 ±4.90l/min, respectively, the difference being statistically significant (P<0.01). Furthermore, if we assume the presence of ventilatory depression to be due to tissue fall resulting from an increase in cerebral blood flow caused by hypoxia, the magnitude of central hypoxic-hypercapnic interaction was estimated to be as great as the value of .     

Factors which alter the relationship between ventilation and carbon dioxide production during exercise in normal subjects

The slope of the linear relationship between ventilation and carbon dioxide production has been thought to indicate that is one of the major stimuli to . A group of 15 normal subjects undertook different incremental treadmill exercise protocols to explore the relationship between and . An incremental protocol using 1 instead of 3-min stages of exercise resulted in an increase in the to ratio [26.84 (SEM 1.23) vs 31.08 (SEM 1.36) (P < 0.008) for the first stage, 25.24 (SEM 0.86) vs 27.83 (SEM 0.91) (P < 0.005) for the second stage and 23.90 (SEM 0.86) vs 26.34 (SEM 0.81) (P = 0.001) for the third stage]. Voluntary hyperventilation to double the control level of during exercise resulted in an increase in the to slope [from 21.3 (SEM 0.71) for the control run to 35.1 (SEM 1.2) for the hyperventilation run (P < 0.001)]. Prolonged hyperventilation (5 min) during exercise at stage 2 of the Bruce protocol resulted in a continuted elevation of and the slope. A steady state of and metabolic gas exchange can only be said to have been present after at least 3 min of exercise. Voluntary hyperventilation increased the slope of the relationship between and . End-tidal carbon dioxide fell, but remained within the normal range. These results would suggest that a non-carbon dioxide factor may have been responsible for the increase we found in during exercise, and that factors other than increased dead space ventilation can cause an increased ventilation to slope, such as that seen in some pathophysiological conditions, such as chronic heart failure.     

Changes of ventilation and ventilatory response to hypoxia during the menstrual cycle

The relationship between change in hypoxic sensitivity in respiration, defined as increment in ventilation per drop of arterial O₂ saturation , with the phase change from follicular to luteal and those in resting pulmonary ventilation , mean inspiratory flow (V _T/T _I), alveolar partial pressures of CO₂ and O₂ ( and , respectively) and body temperature was studied in 10 women. There was a significant relationship between % increase in hypoxic sensitivity and decrement of resting that occurred in the luteal phase. However, no significant relationships were observed between change in hypoxic sensitivity and those in the remaining parameters studied. The intersubject variation in % increase in resting during the luteal phase was not associated with that in % increase in hypoxic sensitivity. The results indicate that the contribution of increased hypoxic sensitivity to increasing during the luteal phase is variable among subjects. Reasons for the increase in hypoxic sensitivity with hypocapnia are discussed.     

Analysis of alveolar PCO 2 control during the menstrual cycle

We attempted to analyze how is regulated during progesterone-induced hyperventilation in the luteal phase. A model for the CO₂ control loop was constructed, in which the function of the CO₂ exchange system was described as and that of the CO₂ sensing system as . Using this model, we estimated (1) the primary increase in produced by progesterone stimulation and (2) the effectiveness (E) of the loop to regulateP _{A CO 2}, defined as P _{A CO 2} (op)/P _{A CO 2} (cl) in which op signifies open-loop and cl, closed-loop. These respiratory variables were investigated throughout the menstrual cycle in 8 healthy women. During the luteal phase, on average, increased by 9.4% andP _{A CO 2},B andH decreased by 0.33 kPa (2.5 mm Hg), 0.47 kPa (3.5 mm Hg) and 13.6%, respectively, whileS and did not change significantly. (op) increased progressively on successive days of the luteal phase whileE remained unchanged at a value of 7.9, thus there was a progressive decrease inP _{A CO 2}. The decrease inH was considered to lessen P _{A CO 2} (op) and so reduce the final deviation ofP _{A CO 2} (P _{A CO 2} (cl)) during the luteal phase. The decrease inB was found to be dependent on (op).     

The role of the vagus nerves in the respiratory response to CO2 under hyperoxic conditions

Summary In anesthetized rabbits rebreathing oxygen the respiratory and circulatory responses to increased were determined repeatedly in the same animal before and after inactivation of the vagus nerves by cold blocking and finally sectioning. In some animals responses were also obtained by blocking the vagi during respiration of constant mixtures of CO₂ and O₂. With intact vagi the response curve was, on the average, practically linear up to an increase of the by 27 Torr. Inactivation of the vagi caused a small increase of the resting ventilatory minute volume during the initial breathing of pure oxygen, and a corresponding decrease of the resting . In the range of small increases of the response curve was significantly steepened and shifted to higher ventilatory values by the inactivation. With greater increases, the slope of the response with inactivated vagi was flatter and shifted to lower ventilatory values as compared with intact vagi. These effects were the result of corresponding changes of the response curves for tidal volume and respiratory rate: Inactivation considerably steepened the response at low values of while flattening the response at high values, whereas the curve was only depressed at all stages of hypercapnia. The results were principally the same whether the carotid sinus nerves were intact or sectioned. Vagal inactivation had only little influence on the reactions of systemic blood pressure and heart rate to the increase of . It is concluded that vagal reflexes, possibly from stretch receptors of the lungs, modify the ventilatory efficacy of the central chemosensitive drive of respiration in the rabbit.Supported by grant Wi 165 from the Deutsche Forschungsgemeinschaft.     

Quantitative aspects of respiration and glycolysis in the white cells of human blood

Summary The study of the velocity of respiration and glycolysis of various forms of human leukocytes deomonstrated that these indicators of metabolism of white blood cells may be quantitatively compared with these indicators found in case of human carcinoma and sarcoma (formerly established by O. Warburg and his collaborators. Coefficints and were also found to be very similar in cancer cells and leukocytes. In case of leukocytes of normal blood the ratio the ratio .As to the leukocytes of patients with chronic myeloid leukemia these values equalled; 5, 13, 2; 23, 3; 4.7 and 2.6, respectively. In case of lymphocytes the values of respiration and glycolysis were: . The ratio .Presented by Active Member of the AMN SSSR A. I. Serebrov)     

Ventilatory response during incremental exercise tests in weight lifters and endurance cyclists

Summary The effect of a progressively increasing work rate (15 W·min^–1) up to exhaustion on the time course of O₂ uptake ( ), ventilation ( ) and heart rate (HR) has been studied in weight lifters (WL) in comparison to endurance cyclists (Cycl) and sedentary controls (Sed). and were measured as average value of 30-s intervals by a semiautomatic open circuit method. was 2.55±0.33; 4.29±0.53 and 2.86±0.19·min^–1 in WL, Cycl and Sed respectively. With time and work rate, while and HR increased linearly, changed its slope at two levels. The 1st change occured at a work load corresponding to a mean (± SD) of 1.50±0.26; 1.93±0.34; and 1.23±0.14 l·min^–1 in WL, Cycl, and Sed respectively. values corresponding to the second change of slope were 2.18±0.32 in WL; 3.48±0.53 in Cycl and 2.17±0.28 l·min^–1 in Sed. The first change of slope might be the consequence of the different readjustment of on-response and hence of early lactate in the different subjects. The second change seems to be comparable to the conventional anaerobic threshold and is achieved in all subjects when vs time slope is 7–10 l·min^–1/min of exercise.This work has been supported in part by a grant from the Italian National Research Council (CNR)     

Aerobic power and pubertal peak height velocity in Belgian boys

Summary To determine the cardiorespiratory response to maximal exercise before, during and after the pubescent growth spurt, thirty boys were tested at yearly intervals over a period of six consecutive years. For each individual, peak height velocity (PHV) was determined. The age at PHV (¯X= 13.6 years) was taken as a standard of maturation. The results from all subjects at 1.5 and 0.5 years before and 0.5 and 1.5 years after PHV are presented. The highest oxygen uptake ( ) obtained during an incremental bicycle ergometer test to voluntary exhaustion was taken as peak oxygen uptake ( peak). Across each of the four years studied, mean peak (min=49.6; max=52.5 ml·kg^–1·min^–1) and mean heart rate (HR) at peak (min=190; max=192) did not change significantly as a function of PHV. On the other hand, the respiratory quotient at peak increased considerably from mean minima and maxima of 0.99 and 1.01 before PHV to 1.07 and 1.10 after PHV. Ventilatory equivalent for ( ), taken as an indicator of ventilatory economy, seemed to be unaffected by the maturation process. The steepest increase in circumpubertal oxygen pulse was found one year after PHV. Average stability coefficients (¯r), calculated from the inter-years correlations were high for height (¯r=0.95), weight (¯r=0.92), HR at peak (¯r=0.74), peak in 1/min (¯r=0.71), oxygen pulse (¯r=0.68) and tidal volume (¯r=0.64).     

Diffusion-limited gas mixing in the lung and its consequences for transpulmonary gas transport

The ratio of alveolar ventilations of He and SF₆ ( ) was determined in 7 healthy male subjects at rest and at three different levels of exercise on a bicycle ergometer (75, 150 and 225 W). This ratio was calculated from the ratio of the specific ventilations for these gases which were obtained from the decay of the end-tidal partial pressures of He and SF₆ during a simultaneous, multiple-breath washout. In all experiments, for He was larger than for SF₆. On the average, was equal to 1.09, and the mean values of this ratio at rest and at the three levels of exercise were not significantly different. Therefore, the difference in for He and SF₆ increased with increasing work load. Further, we used the mean value obtained for , to calculate the ratio of excretion values (E₁/E₂) for pairs of hypothetical tracer gases with equal blood-gas partition coefficients and with different diffusivities in the gas phase. E₁/E₂ ranged from anity for =0 to about 1.08 for =10. At a given , E₁/E₂ decreased with increasing ventilation-perfusion ratio of the lung. Thus, the difference between the excretion values of light and heavy tracer gases will be most pronounced under rest conditions and for gases that are well soluble in blood.     

Precision of ventilatory and gas exchange alterations as a predictor of the anaerobic threshold

Summary Anaerobic threshold has been defined as the oxygen uptake ( ) at which blood lactate (La) begins to rise systematically during graded exercise (Davis et al. 1982). It has become common practice in the literature to estimate the anaerobic threshold by using ventilatory and/or gas exchange alterations. However, confusion exists as to the validity of this practice. The purpose of this study was to examine the precision with which ventilatory and gas exchange techniques for determining anaerobic threshold predicted the anaerobic threshold resolved by La criteria. The anaerobic threshold was chosen using three criteria: (1) systematic increase in blood La (AT_La), (2) systematic increase in ventilatory equivalent for O₂ with no change in the ventilatory equivalent for CO₂ ( ), and (3) non-linear increase in expired ventilation graphed as a function of ( ). Thirteen trained male subjects performed an incremental cycle ergometer test to exhaustion in which the load was increased by 30 W every 3 minutes. Ventilation, gas exchange measures, and blood samples for La analysis were obtained every 3rd min throughout the test. In five of the thirteen subjects tested the anaerobic threshold determined by ventilatory and gas exchange alterations did not occur at the same as the AT_La. The highest correlation between a gas exchange anaerobic threshold and AT_La was found for and was r=0.63 (P<0.05). These data provide evidence that the AT_La and do not always occur simultaneously and suggest limitations in using ventilatory or gas exchange measures to estimate the AT_la.     

Changes in skeletal muscle oxygenation during incremental exercise measured with near infrared spectroscopy

To determine the change in muscle oxygenation in response to progressively increasing work rate exercise, muscle oxyhemoglobin + oxymyoglobin saturation was measured transcutaneously with near infrared spectroscopy in the vastus lateralis muscle during cycle ergometry. Studies were done in 11 subjects while gas exchange was measured breath-by-breath. As work rate was increased, tissue oxygenation initially either remained constant near resting levels or, more usually, decreased. Near the work rate and metabolic rate where significant lactic acidosis was detected by excess CO₂ production (lactic acidosis threshold, LAT), muscle oxygenation decreased more steeply. As maximum oxygen uptake ( ) was approached, the rate of desaturation slowed. In 8 of the 11 subjects, tissue O₂ saturation reached a minimum which was sustained for 1–3 min before was reached. The LAT correlated with both the (r = 0.95,P < 0.0001) and the work rate (r = 0.94,P < 0.0001) at which the rate of tissue O₂ desaturation accelerated. These results describe a consistent pattern in the rate of decrease in muscle oxygenation, slowly decreasing over the lower work rate range, decreasing more rapidly in the work rate range of the LAT and then slowing at about 80% of , approaching or reaching a minimum saturation at .     

Total muscle mitochondrial volume in relation to aerobic capacity of horses and steers

The relationship between maximal oxygen consumption rate ( ) and mitochondrial content of skeletal muscles was examined in horses and steers (n=3 each). Samples of the heart left ventricle, diaphragm,m. vastus medialis, m. semitendinosus, m. cutaneous thoracicus andm. masseter, as well as samples of muscles collected in a whole-body sampling procedure, were analyzed by electron microscopy. per kilogram body mass was 2.7× greater in horses than steers. This higher was in proportion to the higher total volume of mitochondria in horse versus steer muscle when analyzed from the whole-body samples and from the locomotor muscle samples. In non-locomotor muscles, total mitochondrial volume was greater in horses than steers, but not in proportion to their differences in . The of the mitochondria was estimated to be close to 4.5 ml O₂·ml^–1 mitochondria in both species. It is concluded that in a comparison of a highly aerobic to a less aerobic mammalian species of similar body size, a higher oxidative potential may be found in all muscles of the more aerobic species. This greater oxidative potential is achieved by a greater total volume of skeletal muscle mitochondria.     

Use of oxygen uptake recovery curve to predict peak oxygen uptake in upper body exercise

A group of 18 well-trained white-water kayakers performed maximal upper body exercise in the laboratory and during.a field test. Laboratory direct peak oxygen uptake ( ) values were compared, firstly by a backward extrapolation estimation and secondly by an estimation calculated from measured during the first 20 s of exercise recovery. Direct peak correlated with backward extrapolation (r=0.89), but the results of this study showed that the backward extrapolation method tended to overestimate significantly peak by [0.57 (SD 0.31) 1·min^–1 in the laboratory, and 0.66 (SD 0.33) 1·min^–1 in the field,P<0.001]. The measured during the first 20 s of recovery, whether the exercise was performed in the laboratory or in the field, correlated well with the laboratory direct peak (r=0.92 andr=0.91, respectively). The use of the regression equation obtained from field data _2f20s, that is peak ₂=0.23+1.08 _2f20s, gave an estimated peak ₂, the mean difference of which compared with direct peak was 0.22 (SD 0.13) 1·min^–1. In conclusion, we propose the use of a regression equation to estimate peak from a single sample of the gas expired during the first 20 s of recovery after maximal exercise involving the upper part of the body.     

A model for studying the distortion of muscle oxygen uptake patterns by circulation parameters

Summary The transmission of muscle oxygen uptake patterns to the pulmonary site is a basically nonlinear process during unsteady state exercise. We were mainly interested in three questions concerning the dynamic relationship between power input and pulmonary output: 1. To what extent can linear system analysis be applied? 2. What is the relative influence of muscle on pulmonary as compared to other parameters such as muscle perfusion kinetics? 3. To what extent does pulmonary reflect muscle ? Investigations were performed by means of a mathematical model including a muscle compartment and two serial, flow-varying time delays. The non-exercising parts of the body were. incorporated as one term for perfusion and one for . Parameters were adjusted so as to represent a reference state of aerobic exercise while monofrequent sinusoidal changes in aerobic metabolism were used as forcing signals. The following answers were derived from the simulations: 1. Non-linear distortions of the signals are negligible provided that analyses are not driven too far into the higher frequency range (periods shorter than about 1 min). 2. Variations of muscle kinetics have greater effects on pulmonary than changes of perfusion kinetics or venous volume. This finding applies irrespective of whether or not pulmonary closely reflects muscle 3. Small differences in the time constants for muscle perfusion and muscle are a major prerequisite if pulmonary , kinetics are to be taken as correct estimates of muscle kinetics. High basal muscle perfusion, small perfusion changes and small venous volumes between muscle and lungs are further factors reducing dynamic distortions of the muscle signal.     

Energy sources in alpine skiing (giant slalom)

Summary The energy cost of a giant slalom event was measured in eight skiers of national level. The lap lasted on average 82 s. was measured during the first, the second and the last third of the lap in different trials and also during recovery from a complete lap. Blood lactate was measured at the end of a lap. From the data obtained it was possible to calculate that: a) , as measured during the lap, would correspond at steady state to 80% of the of the subjects; b) the total metabolic power delivered during the lap should be equal to about 72ml O₂·kg^–1·min^–1, corresponding to 120% of of the subjects. Considering the short duration of the trial and the power output delivered during maximal efforts on a bicycle ergometer, it appears that the giant slalom is not a very high energy demanding event.Preliminary results of this work have been presented at the XXII. World Congress on Sport Medicine, Vienna 1982     

Numerical analysis and linear theory of pulsatile flow in cylindrical deformable tubes: The testing of a numerical model for blood flow calculation

The purpose of this paper is to present standard results on the effect of nonlinearities on the computed pulsatile flow in a cylindrical distensible tube as a first stage in the calculation of flow in a tapered tube and blood flow in arteries. The calculations are made using the pressure-radius relationship of a rubber tube with no longitudinal motion and for a linearised relationship. The one-dimensional equations of motion are solved by the method of finite differences. The values of skin friction that are incorporated are determined from the vorticity and continuity equations for a rigid tube and a correction made to the current diameter at each time step. The accuracy of the results is assessed and the effect of varying parameters investigated. The method is applied to a segment of an infinite tube for which the linear analytical solution is available. The characteristics of the velocity wave calculated from an input pressure wave are presented as departures from the linear theory values of these characteristics, the wave speed, flux and transmission factor per wavelength. Computations are made at values of non-dimensional frequency (Stokes number α) of about 3 and 10. It is concluded that as far as physiological application is concerned (i.e. small amplitude and long wavelength) the results of linear theory are a very good first approximation for the cylindrical tube. At α=10, the relative departure of wave speed is about 0·5 times the relative diameter amplitude ( amplitude/mean diameter) when the pressure-radius relation is linear and the pressure and velocity waves have the same characteristics. At α=3 the corresponding wave speed departure is about 0·1 . The relative departure of the flux is less than 0·05 at α=3 and about 0·5 at α=10. The transmission coefficient has a relative departure of less than 0·05 at α=10 and its relative increase at α=3 is about 0·3 .     

Exercise-induced changes in blood ammonia levels in humans

Summary Five male and two female subjects each performed a maximal aerobic capacity ( ) test, and two to four submaximal aerobic exercise bouts (requiring approximately 50 and 80% of the individual's measured ) on a motor-driven treadmill. Pre-exercise resting oxygen uptakes ( ) and heart rates were determined and a venous blood sample drawn prior to each work session. These same measurements were repeated at 4, 15, 30, and 45 min of the resting recovery period that followed each exercise experiment. Additionally, at the 30th min of each 45-min submaximal exercise, another peripheral venous blood sample was drawn following determination of and heart rate. In all blood samples, the hematocrit and concentrations of ammonia, lactate, pyruvate, glucose, hemoglobin, and total plasma proteins were measured.A significant exponential relationship was observed betwen blood ammonia levels and for all sample periods (pre-exercise rest, exercise, and post-exercise recovery). Peripheral venous blood ammonia levels were significantly correlated with levels of pyruvate and lactate, as these latter substrates exhibited a similar exponential relationship with as was observed with ammonia.This work was supported in part by the Air Force Office of Scientific Research, Air Force Systems Command, Grant AFOSR 73-2455 and by the National Institutes of Health, Grant NIH HD00235-6     

Acute altitude exposure and altered acid-base states

Summary This study examined the influence of acute altitude (AL) exposure alone or in combination with metabolic acid-base manipulations on the exercise ventilatory and blood lactate responses. Four subjects performed a 4 min, 30 W incremental test to exhaustion at ground level (GL) and a 4 min, 20 W incremental test during three acute exposures to a simulated altitude of 4200 m; (i) normal (NAL), (ii) following 0.2 g·kg^–1 ingestion of sodium bicarbonate (BAL), and (iii) following 0.5 g·day^–1 ingestion of acetazolamide for 2 days prior to exposure (AAL). increased progressively throughout the incremental tests at AL and the minimum value was not related to a change in the blood lactate response. In contrast, the decreased initially to reach a minimum value at the same power output for each altitude trial and was related to a lactate threshold defined by a log-log transformation (r=0.78). This transformation of the blood lactate data was not influenced by the altered acid-base states. The relative exercise intensity corresponding to both a lactate of 1 mM and an absolute lactate of 4 mM was significantly increased during the AAL (79.9±12.9 and 93.9±13.7% , respectively) compared with NAL (59.1±5.5 and 78.0±5.8% , respectively). These data suggest that strong relationships exist between the ventilatory and blood lactate response during AL exposure and altered acid-base states. Further, it is concluded that, unless the acid-base status is known, the use of an absolute or lactate value to compare submaximal exercise should be interpreted with caution.     

Ventilatory response to CO2 at rest and during positive and negative work in normoxia and hyperoxia

Summary Ventilation versus alveolar relationships were determined by the steady-state method in 6 normal male subjects at rest and during positive and negative work at one load in both normoxic and hyperoxic condition. In 5 subjects the slopes of the lines during positive and negative work increased in normoxia as compared with rest. This effect was less evident in hyperoxia. It was also found that the slopes of the lines in positive and in negative work were about the same in both normoxic and hyperoxic conditions. Oxygen uptake and CO₂ production during positive work is higher than during negative work.These results suggest that: 1) the disagreement between various authors on the change of the slope of the line may be due to the differences in the method of calculation of the slope or the method of the determination of lines; 2) the stimuli from the muscle spindles in the working muscle during exercise probably do not contribute to the increase in ventilatory response to CO₂; 3) the increased slope of the normoxic line during exercise may be due to the interaction of several factors such as impulses from working muscles, chemosensitivity of central or peripheral chemoreceptors, adrenal-sympathetic pathways or temperature; 4) respiratory oscillations of or do not seem to influence the respiratory response to CO₂.This study was supported in part by a grant from the Netherlands Organization for the Advancement of Pure Research (Z.W.O.)     

Effects of estrus cycle on thermoregulatory responses during exercise in rats

Summary In female rats, rectal temperature (T _re), tail vasomotor response, oxygen uptake , and carbon dioxide production were measured in proestrus and estrus stages during treadmill running at two different speeds at an ambient temperature (T _a) of 24° C. Experiments were performed at 2.00–6.00 a.m., when the difference inT _re was greatest between the two stages;T _re at rest in the estrus stage was 0.54° C higher than in the proestrus stage. In a mild warm environment, thresholdT _re for a rise in tail skin temperature (T _tail) was also higher in the estrus stage than in the proestrus stage. In contrast, no difference was seen in the thresholdT _re and steady stateT _re at the end of exercise between proestrus and estrus stages. These values were higher at the higher work intensity. was also similar between the two stages, except in the second 5 min after the beginning of exercise, when was greater andT _re rose more steeply in the proestrus stage. These data indicate that deep body temperature during exercise is regulated at a certain level depending on the work intensity and is not influenced by the estrus cycle.This study was supported in part by a Grant-in Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (Grant No. 62480114)